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GU Cancers 2018 | Immunotherapy for prostate, bladder and kidney cancer

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Elizabeth Plimack

In this video, Elizabeth Plimack, MD, from Fox Chase Cancer Center, Philadelphia, PA, discusses the progress made in prostate, bladder and kidney cancer. There have been significant advances in immunotherapeutic options, particularly for the treatment of bladder and kidney cancers. Speaking from the 2018 Genitourinary Cancers Symposium, held in San Francisco, CA, Dr Plimack mentions the challenges to overcome with non-responders and the different combinations that can be tested, particularly those including checkpoint inhibitors.

Transcript (edited for clarity):

Immunotherapy obviously has been one of the biggest developments in oncology in the last few years, and it’s being explored in prostate, kidney, and bladder cancer, but in different ways.
So with prostate cancer, I think we’re a little bit behind, we need to learn how to make the microenvironment amenable to immunotherapeutic intervention, and we have very little data to go on but a lot of hypotheses, trials, and combinations ongoing looking at biomarkers and combinations...

Immunotherapy obviously has been one of the biggest developments in oncology in the last few years, and it’s being explored in prostate, kidney, and bladder cancer, but in different ways.
So with prostate cancer, I think we’re a little bit behind, we need to learn how to make the microenvironment amenable to immunotherapeutic intervention, and we have very little data to go on but a lot of hypotheses, trials, and combinations ongoing looking at biomarkers and combinations.
In bladder cancer, immunotherapy represents the first approval of a new agent in decades, and those are the PD1 and PD-L1 inhibitors in bladder cancer, so that was dramatic for us in 2016 when the first ones were approved. Now that we moved beyond that, we’re looking at how durable the responses are and most importantly, how we can change patients who are refractory to these immunotherapies into responders, because we know that response is only occurring in about 20% of patients and generally, that’s the same group that have long term benefit from them. But what we’ve seen which is great is some patients with bladder cancer living long, healthy, lives, free of side effects, which is something we never really could have imagined before.
So it has changed the field, it’s helped a lot of patients, we want immunotherapy to help more patients with bladder cancer. Ways that we’re looking at that are of course, combination strategies, so chemotherapy-immunotherapy combinations, immunotherapy-immunotherapy combinations with IDO inhibitors and with CTLA-4 inhibitors, and then novel agents after immunotherapy doesn’t work, like enfortumab vedotin is one that’s promising, so that’s not specifically an immunotherapy, but we’re looking on all those fronts in bladder cancer. In kidney cancer, we have had checkpoint inhibitors approved now for a few years nivolumab specifically, but we’re seeing really interesting data combining nivolumab and ipilimumab, and combining PD1 inhibitors with a TKI inhibitor, specifically axitinib, seems to combine the best, so we’re seeing now the results of those Phase III trials coming out. We saw ipilimumab and nivolumab, that Phase III trial came out at ESMO.
At this meeting, we’re going to see the first VEGF/PDL1 combination in Phase III, that’s bevacizumab, atezolizumab versus sunitinib, and so from these randomized trials, we can really see the advantage that adding immunotherapy brings to VEGF inhibition for instance, or adding CTLA-4 therapy brings to PD1-targeted therapy. So this is where we’re seeing really practice-changing Phase III data.
So in kidney cancer, the question is; it’s an embarrassment of riches, we have a lot of drugs that work, which one do we use first, how can we sequence these to give each patient the longest survival, and ideally for some of them, achieve close to cure or treatment-free survival, right now it’s a minority of patients we’re hoping to expand on.

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